Olfactory impairment as an early marker of Parkinson’s disease in REM sleep behaviour disorder: a systematic review and meta-analysis

Lyu, Zhihong; Zheng, Shuxin; Zhang, Xiaoyuan; Mai, Yiling; Pan, Jiyang; Hummel, Thomas; Hähner, Antje; Zou, Lai‐quan

doi:10.1136/jnnp-2020-325361

Cited by 17 publications

(14 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Olfactory dysfunction typically presents as one of the earliest events. It is the most specific predictor among nonmotor manifestations for recognising patients at short-term risk for PD and DLB 8. Additionally, the severity of autonomic symptoms was suggested to be associated with an accelerated rate of phenoconversion and putaminal DAT abnormalities in patients with iRBD 5.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Possible predictors of phenoconversion in isolated REM sleep behaviour disorder: a systematic review and meta-analysis

Wang

Chen

et al. 2021

J Neurol Neurosurg Psychiatry

View full text Add to dashboard Cite

BackgroundA number of promising biomarkers for predicting imminent α-synucleinopathies have been suggested in isolated rapid eye movement sleep behaviour disorder (iRBD). However, existing evidence is conflicting without quantitative evaluation.MethodsPubMed, Web of Science and ClinicalTrials.gov were searched through June 2021 to identify possible predictors of phenoconversion from iRBD to Parkinson’s disease (PD). The pooled HRs and standardised mean differences (SMDs) with 95% CIs were calculated using fixed-effects or random-effects model.ResultsA total of 123 studies were included in the meta-analysis. Significant motor dysfunction (HR 1.83, 95% CI 1.33 to 2.51, I2=86.8%, p<0.001), constipation (HR 1.52, 95% CI 1.26 to 1.84, I2=8.3%, p=0.365), orthostatic hypotension (HR 1.93, 95% CI 1.05 to 3.53, I2=54.9%, p=0.084), hyposmia (HR 2.78, 95% CI 1.83 to 4.23, I2=23.9%, p=0.255), mild cognitive impairment (HR 2.27, 95% CI 1.58 to 3.27, I2=0%, p=0.681) and abnormal colour vision (SMD −0.34, 95% CI −0.63 to −0.05, I2=45.6%, p=0.087) correlated with susceptibility to PD. The process can also be traced by putaminal dopamine transporter imaging (HR 2.60, 95% CI 1.94 to 3.48, I2=0%, p=0.781) and tonic electromyographic activity (HR 1.50, 95% CI 1.04 to 2.15, I2=70%, p=0.018).ConclusionsThe predictive value of each biomarker was initially highlighted with comprehensive evaluation. Combining specific predictors with high sensitivity is promising for detecting phenoconversion in the prodromal stage. Large-scale and multicentre studies are pivotal to extend our findings.

show abstract

Section: Discussionmentioning

confidence: 99%

“…Supplementary neuroimaging, electrophysiological, biofluid and genetic biomarkers are also proposed as promising candidates 7. However, limited clinical trials have attested to the reliability of those markers with unsolved discrepancies, and only one meta-analysis identified the predictive value of hyposmia 8…”

Section: Introductionmentioning

confidence: 99%

Possible predictors of phenoconversion in isolated REM sleep behaviour disorder: a systematic review and meta-analysis

Wang

Chen

et al. 2021

J Neurol Neurosurg Psychiatry

View full text Add to dashboard Cite

show abstract

“…Based on the evidence of injury-induced neurogenesis in the olfactory epithelium, it is logical to presume that accumulated physiological deterioration, as an outcome of lifestyle, could negatively influence neurogenesis in the olfactory epithelium causing olfactory decline through multiple cell types. Emerging experimental evidence even indicates the participation of non-neuronal cells in olfactory processing and odor perception that precede neurodegenerative pathology [ 44 , 115 ]. Therefore, the overall evaluation of olfactory dysfunction in combination with additional symptoms while considering multiple environmental and genetic factors for added risk could provide avenues for early therapeutic intervention.…”

Section: Discussionmentioning

confidence: 99%

“…Rapid eye movement sleep behavior disorder (RBD) is an additional well-established clinical marker of PD. It is marked by an increment in odor threshold and significant impairment in odor identification and discrimination [ 115 ]. However, RBD is a recently identified marker where additional physiological and molecular information is still very limited.…”

Section: Neurodegenerative Diseasesmentioning

confidence: 99%

The Olfactory System as Marker of Neurodegeneration in Aging, Neurological and Neuropsychiatric Disorders

Bhatia‐Dey

Heinbockel

2021

IJERPH

View full text Add to dashboard Cite

Research studies that focus on understanding the onset of neurodegenerative pathology and therapeutic interventions to inhibit its causative factors, have shown a crucial role of olfactory bulb neurons as they transmit and propagate nerve impulses to higher cortical and limbic structures. In rodent models, removal of the olfactory bulb results in pathology of the frontal cortex that shows striking similarity with frontal cortex features of patients diagnosed with neurodegenerative disorders. Widely different approaches involving behavioral symptom analysis, histopathological and molecular alterations, genetic and environmental influences, along with age-related alterations in cellular pathways, indicate a strong correlation of olfactory dysfunction and neurodegeneration. Indeed, declining olfactory acuity and olfactory deficits emerge either as the very first symptoms or as prodromal symptoms of progressing neurodegeneration of classical conditions. Olfactory dysfunction has been associated with most neurodegenerative, neuropsychiatric, and communication disorders. Evidence revealing the dual molecular function of the olfactory receptor neurons at dendritic and axonal ends indicates the significance of olfactory processing pathways that come under environmental pressure right from the onset. Here, we review findings that olfactory bulb neuronal processing serves as a marker of neuropsychiatric and neurodegenerative disorders.

show abstract

“…UPSIT performance was found to be a predictor of PD-MCI in this study, and this result is corroborated by several other studies (Hu et al, 2014 ; Fullard et al, 2016 ; Hogue et al, 2018 ; Roos et al, 2019 ; Pekel et al, 2020 ). Moreover, olfactory deficits were found to be a risk and predictor of dementia and PD in iRBD patients (Postuma et al, 2019 ; Lyu et al, 2021 ). It has been reported that PD-MCI is more likely to be associated with severe olfactory impairment than PD patients with normal cognition (Park et al, 2018 ), and an imaging study found entorhinal cortex atrophy in early, drug-naive PD patients with MCI (Jia et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Development and Validation of a Prognostic Model for Cognitive Impairment in Parkinson’s Disease With REM Sleep Behavior Disorder

Chen

et al. 2021

Front. Aging Neurosci.

View full text Add to dashboard Cite

The presentation and progression of Parkinson’s disease (PD) are not uniform, but the presence of rapid eye movement sleep behavior disorder (RBD) in PD patients may indicate a worse prognosis than isolated PD. Increasing evidence suggests that patients with comorbid PD and RBD (PD-RBD) are more likely to develop cognitive impairment (CI) than those with isolated PD; however, the predictors of CI in PD-RBD patients are not well understood. This study aimed to develop a prognostic model for predicting mild cognitive impairment (MCI) in PD-RBD patients. The data of PD-RBD patients were extracted from the Parkinson’s Progression Markers Initiative study (PPMI), and the sample was randomly divided into a training set (n = 96) and a validation set (n = 24). PD-MCI as defined by the level II Movement Disorder Society (MDS) diagnostic criteria was the outcome of interest. The demographic features, clinical assessments, dopamine transporter (DAT) imaging data, cerebrospinal fluid (CSF) analyses and genetic data of PD patients were considered candidate predictors. We found that performance on the University of Pennsylvania Smell Identification Test (UPSIT), the mean signal and asymmetry index of the putamen on DAT imaging, p-tau/α-syn and p-tau in CSF, and rs55785911 genotype were predictors of PD-MCI in PD-RBD patients. A C-index of 0.81 was obtained with this model, and a C-index of 0.73 was obtained in the validation set. Favorable results of calibrations and decision curve analysis demonstrated the efficacy and feasibility of this model. In conclusion, we developed a prognostic model for predicting MCI in PD-RBD patients; the model displayed good discrimination and calibration and may be a convenient tool for clinical application. Larger samples and external validation sets are needed to validate this model.

show abstract

Olfactory impairment as an early marker of Parkinson’s disease in REM sleep behaviour disorder: a systematic review and meta-analysis

Cited by 17 publications

References 61 publications

Possible predictors of phenoconversion in isolated REM sleep behaviour disorder: a systematic review and meta-analysis

Possible predictors of phenoconversion in isolated REM sleep behaviour disorder: a systematic review and meta-analysis

The Olfactory System as Marker of Neurodegeneration in Aging, Neurological and Neuropsychiatric Disorders

Development and Validation of a Prognostic Model for Cognitive Impairment in Parkinson’s Disease With REM Sleep Behavior Disorder

Contact Info

Product

Resources

About